In vivo effects of FFA on hepatic glucose production remain equivocal and controversial. We have previously provided evidence suggesting that this may be due to two separate actions of FFA with opposite effects on hepatic glucose production (HGP). Namely, 1) an increase in HGP caused by stimulation of gluco-neogenesis and 2) a decrease in HGP caused by FFA mediated stimulation of insulin secretion. The hypothesis is that FFA mediated stimulation of insulin secretion starts to fail at some point during the development of NIDDM.